Astaxanthin (3,3′-dihydroxy-β,βcarotene-4,4′-dione, ATX) is an organic red pigment belonging to the xanthophyll family (oxygenated carotenoids), containing both hydroxyl and ketone functional groups. ATX possesses the empiric formula of (C40H52O4) and is produced by microorganism such as fungi and alga, and is currently used as a health/nutritional food supplement.
ATX has self-limited absorption orally, antibacterial properties and antithrombotic properties in various animal models. ATX is a potent antioxidant, and may be beneficial in cardiovascular, immune, inflammatory and neurodegenerative diseases.
Implantable medical devices, such as heart valves, prosthetic joints and intravascular catheters, are at risk of becoming a source of infection via surface-adhering bacteria. As the lumen of the device is coated by microorganisms, nutrient rich blood products provide ideal growth niche for bacteria as it passes through or around the device. Microorganisms become embedded on the device to form thereon a biofilm resistant to conventional antimicrobial treatments. Biofilm formation leads to the development of a fibrin sheath, infection and thrombus formation.
The requirements of medical devices include: 1) biocompatibility; 2) strong evidence of anti-infective efficiency; 3) fixation and durability; and 4) mechanical characteristics that match the application. Further, medical devices such as a dialysis catheter should additionally prevent thrombus and fibrin sheath formation; and provide a broad-spectrum antimicrobial activity. Thus, antibacterial and antithrombotic coating for medical devices is needed.
Middleton et al. (Organocatalytic synthesis of astaxanthin-containing ploy(lactide)s, Polym. Chem., 2011, 2, 595-600A), describe the synthesis of astaxanthin-containing poly(lactide)s by the ring-opening polymerization of lactide initiated from residual alcohol groups on astaxanthin using a thiourea/tertiary amine catalyst. The astaxanthin was used as a catalyst for the reaction, and as such remained in relatively small quantities in the poly(lactic acid) chains prepared, compared to the amount of lactic acid therein. Low molecular weight polylactides of up to 30 kD Mw were synthesized, where the higher molecular weight polymers led to smaller content of astaxanthin catalyst (210 lactide molecules to one ATX). Additionally, the reaction times were several days, which is commercially impractical.
The use of ATX in clinical applications is limited, mainly to oral application, which, while providing a systemic effect, is not sufficient to treat certain localized conditions, and further, since it has only immediate release effects, it does not provide a desired controlled release treatment, which would enable the treatment of various conditions.
The polyastaxanthin based polymers disclosed herein represent a significant technological step from the astaxanthin-based polymers known in the art. One of the drawbacks of ATX-containing polymers known in the field is that such polymers comprise only a single ATX unit. For example, astaxanthin-containing polylactide is a polymer that comprises polylactide, (—C3H4O2-)n, as the repeating unit and a single ATX unit.
Acknowledgement of the above references herein is not to be inferred as meaning that these are in any way relevant to the patentability of the presently disclosed subject matter.